How kinases control membrane trafficking
We investigate how membranes of the secretory pathway are regulated by signal transduction pathways. Here, we are particularly interested in the role of the protein kinase D family. Specifically, we address how external cues control PKD activity and how the kinase engages its interactors and substrates to coordinate the secretory pathway.
Ultimately, we aim at determining the relevance of PKD in cell growth, polarity, migration and invasion, and stem cell maintenance to understand the impact of dys-regulation of PKD signaling and secretion in human diseases such as cancer and neurodegeneration.
Cell line engineering for improved production of therapeutic proteins
Chinese hamster ovary (CHO) cells are the most commonly used host for biopharmaceutical production. Although transcription and translation strategies have been employed to generate highly productive cell clones, secretion still remains a bottleneck for cellular productivity. By targeting the secretory pathway at multiple levels using synthetic biology tools, we aim to generate highly productive cell lines with predictable performance at an industrially relevant scale.
We employ an interdisciplinary approach combining 2D and 3D cell culture including primary cells from mice and humans, biochemistry, advanced microscopic techniques e.g. TIRF, FRET, and FRAP, image-based high-throughput screening, and in vivo mouse models.
Funded H2020 (MSCA 2019) project: SECRET - A MARIE SKŁODOWSKA-CURIE ACTIONS (MSCA) Innovative Training Network (ITN)
We will be exploring the SECRETory pathway regulation and its contribution to cancer by providing a highly qualified platform for European research training of bright young scientists, with the aim of defining secretory pathway-linked candidate biomarker genes suitable for cancer diagnosis and prognosis.
For details, check out the SECRET-ITN website: https://secret-itn.eu/
Our paper is finally published in PNAS! In this excellent interdisciplinary collaboration with Thomas Leonard and Ronja Reinhard from Max Perutz Labs in Vienna, we uncover the mechanism of phosphorylation-induced PKD activation and show that autophosphorylation of the activation loop occurs in cis.
- Dendritic effects of genetically encoded actin labelling probes in cultured hippocampal neurons. Ignácz A, Nagy-Herczeg D, Hausser A, Schlett K. Molecular Biology of the Cell. 2023. doi: 10.1091/mbc.E22-08-0331
- PKD autoinhibition in trans regulates activation loop autophosphorylation in cis. Reinhardt R, Hirzel K, Link G, Eisler SA, Hägele T, Parson MAH, Burke JE, Hausser A, Leonard TA. Proceedings of the National Academy of Sciences. 2023; 120(7):e2212909120. doi: 10.1073/pnas.2212909120
- Protein Kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons. Oueslati Morales CO, Ignácz A, Bencsik N, Sziber Z, Rátkai AE, Lieb WS, Eisler SA, Szűcs A, Schlett K, Hausser A. Traffic. 2021 Sep 26. doi: 10.1111/tra.12819. Online ahead of print.
- Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs. Pacheco-Fernandez N, Pakdel M, Blank B, Sanchez-Gonzalez I, Weber K, Tran ML, Hecht TK, Gautsch R, Beck G, Perez F, Hausser A, Linder S, von Blume J. J Cell Biol. 2020 Aug 3;219(8):e201907058. doi: 10.1083/jcb.201907058. PMID: 32479594
- Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice. Zhang S, Liu H, Yin M, Pei X, Hausser A, Ishikawa E, Yamasaki S, Jin ZG. Hepatology. 2020 Nov;72(5):1717-1734. doi: 10.1002/hep.31176. PMID: 32048304
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Prof. Dr. Angelika Hausser (apl.), Lab head
Raluca Tamas, PhD (Program manager SECRET-ITN)
Kerstin Ruoff, PhD (Postdoctoral Researcher)
Elena Gutiérrez Galindo, PhD student
Zeynep Hazal Yilmaz, PhD student
Sara Suárez López, PhD Student
Gisela Link, Technical assistant
Elias Stahl, Master Student
Katharina Jursik, Master Student
Applications of students and scientists interested in signal transduction and membrane trafficking, and joining our team are always welcome! Please send your CV and a short summary of your research interests to Angelika Haußer.